Approximately 24,000 new thoracoabdominal aortic aneurysms (TAA/As) are diagnosed in the United States each year. Five-year survival estimates for this population range from 15 to 50%. The majority of patients with TAA/As is in their 60's, 70's, and 80's, and cannot tolerate the daunting physiological insult of open resection. Despite good results in carefully selected patients in centers focusing on aortic surgery, fewer than 2000 per year (10%) are treated surgically, with a nationwide hospital mortality rate of at least 20% and a one-year survival of only 60 to 70%. As a consequence, 90% of patients with TAA/As do not come to surgery because it is anticipated that they will have a prohibitive operative mortality. Endovascular therapy could rescue the majority of these patients if two problems can be solved. The first is to find a way to provide flow to the visceral vessels either by devising a simple system for branched stents from the aorta, or by providing flow from the ascending aorta or iliac arteries (extra-anatomic debranching). The second challenge is to ensure the ability to routinely sacrifice all segmental arteries, (intercostal and lumbar arteries) without spinal cord injury. A number of promising approaches are under way to address the first problem, and the investigations described in this proposal will solve the second. Our studies on cerebral protection have allowed implementation of our findings from the pig model in the clinical setting with excellent results, and during the last few years we have realized that the pig is an equally good model for translational experiments of spinal cord protection. The anatomy of spinal cord perfusion is very similar in the pig and in man, and the pathophysiology of spinal cord ischemia following extensive sacrifice of segmental arteries is also similar. Ligation of all segmental arteries in the pig model is now possible without functional spinal cord injury in more than 50% of the experimental animals. The chronic pig model allows us to study blood flow under a variety of controlled circumstances which simulate the conditions which would prevail clinically during surgical or endovascular therapy. It also enables us to monitor the impact on spinal cord function of various interventions during and following the procedure, and to evaluate the effect of various changes in procedure on functional outcome, anatomy, and on histology. The investigations we propose concern spinal cord hemodynamics, specifically: 1.to utilizes vasculature visualization and microsphere blood flow studies to elucidate the anatomy and physiology of spinal cord perfusion 2. To explore the physiological mechanisms and time course of spinal cord blood flow following extensive segmental artery sacrifice. 3. to develop clinically relevant strategies to minimize ischemia and prevent spinal cord injury during or following surgery or endovascular treatment of extensive TAA/As. PUBLIC HEALTH RELEVANCE The majority of older patients with aneurysms involving both the abdominal and thoracic aorta cannot be treated and consequently die when the aneurysm ruptures. Surgical therapy necessitates an operation of a magnitude that is not tolerated by older patients, and minimally invasive therapy (placement of a stent graft) blocks all the small blood vessels which supply the spinal cord, resulting in paralysis of the lower body. We propose a series of studies to elucidate the anatomy and physiology of the spinal cord circulation because we believe that knowledge will translate directly into patient care, offering hope of cure to the estimated 20,000 Americans who die each year of aneurysm rupture.